Pooled analysis of higher versus lower blood pressure targets for vasopressor therapy septic and vasodilatory shock

Purpose

Guidelines for shock recommend mean arterial pressure (MAP) targets for vasopressor therapy of at least 65 mmHg and, until recently, suggested that patients with underlying chronic hypertension and atherosclerosis may benefit from higher targets. We conducted an individual patient-data meta-analysis of recent trials to determine if patient variables modify the effect of different MAP targets.

Methods

We searched the MEDLINE, EMBASE, and Cochrane Central Register of Controlled Trials for randomized controlled trials of higher versus lower blood pressure targets for vasopressor therapy in adult patients in shock (until November 2017). After obtaining individual patient data from both eligible trials, we used a modified version of the Cochrane Collaboration’s instrument to assess the risk of bias of included trials. The primary outcome was 28-day mortality.

Results

Included trials enrolled 894 patients. Controlling for trial and site, the OR for 28-day mortality for the higher versus lower MAP targets was 1.15 (95% CI 0.87–1.52). Treatment effect varied by duration of vasopressors before randomization (interaction p = 0.017), but not by chronic hypertension, congestive heart failure or age. Risk of death increased in higher MAP groups among patients on vasopressors > 6 h before randomization (OR 3.00, 95% CI 1.33–6.74).

Conclusions

Targeting higher blood pressure targets may increase mortality in patients who have been treated with vasopressors for more than 6 h. Lower blood pressure targets were not associated with patient-important adverse events in any subgroup, including chronically hypertensive patients.

     

Impact of the driving pressure on mortality in obese and non-obese ARDS patients: a retrospective study of 362 cases

Purpose

The relation between driving pressure (plateau pressure-positive end-expiratory pressure) and mortality has never been studied in obese ARDS patients. The main objective of this study was to evaluate the relationship between 90-day mortality and driving pressure in an ARDS population ventilated in the intensive care unit (ICU) according to obesity status.

Methods

We conducted a retrospective single-center study of prospectively collected data of all ARDS patients admitted consecutively to a mixed medical-surgical adult ICU from January 2009 to May 2017. Plateau pressure, compliance of the respiratory system (Crs) and driving pressure of the respiratory system within 24 h of ARDS diagnosis were compared between survivors and non-survivors at day 90 and between obese (body mass index?≥?30 kg/m²) and non-obese patients. Cox proportional hazard modeling was used for mortality at day 90.

Results

Three hundred sixty-two ARDS patients were included, 262 (72%) non-obese and 100 (28%) obese patients. Mortality rate at day 90 was respectively 47% (95% CI, 40–53) in the non-obese and 46% (95% CI, 36–56) in the obese patients. Driving pressure at day 1 in the non-obese patients was significantly lower in survivors at day 90 (11.9?±?4.2 cmH₂O) than in non-survivors (15.2?±?5.2 cmH₂O, p?<?0.001). Contrarily, in obese patients, driving pressure at day 1 was not significantly different between survivors (13.7?±?4.5 cmH₂O) and non-survivors (13.2?±?5.1 cmH₂O, p?=?0.41) at day 90. After three multivariate Cox analyses, plateau pressure [HR?=?1.04 (95% CI 1.01–1.07) for each point of increase], Crs [HR?=?0.97 (95% CI 0.96–0.99) for each point of increase] and driving pressure [HR?=?1.07 (95% CI 1.04–1.10) for each point of increase], respectively, were independently associated with 90-day mortality in non-obese patients, but not in obese patients.

Conclusions

Contrary to non-obese ARDS patients, driving pressure was not associated with mortality in obese ARDS patients.

     

Pathogenesis of systemic scleroderma: immunological aspects

Systemic sclerosis (SSc) is a connective tissue disorder that is characterized by excessive collagen synthesis by fibroblasts and by vascular hyperreactivity and obliteration phenomena. Excessive collagen production is the consequence of abnormal interactions between endothelial cells, fibroblasts and mononuclear cells. Immunological abnormalities are present very early in the development of SSc. Mononuclear cells, particularily macrophages and T lymphocytes play a prominent role in fibroblast activation and collagen synthesis through the cytokines they produce. Thus, lymphocytic infiltrates in the skin and in the lung are preferentially composed of CD8+ T lymphocytes, that produce important amounts of interleukin 4 (IL-4). The effects of IL-4 are added to these of transforming growth factor B (TGF-B) and connective tissue growth factor (CTGF) that stimulate collagen synthesis by fibroblasts. T lymphocytes produce important amounts of gamma interferon (INF-gamma) that is the best inhibitor of collagen synthesis by fibroblasts. However, the inhibitory effect of INF-gamma on collagen synthesis is diminished in SSc patients. Numerous autoantibodies can be evidenced in the serum of SSc patients. Three of them are specific for SSc and mutually exclusive: anti-centromere antibodies (Ab) in limited SSc, anti-Scl70 Ab in diffuse SSc and anti-RNA polymerase III Ab in diffuse SSc with renal involvement. These autoantibodies are good prognosis markers but their pathogenic role remains uncertain.     

Jamming of prosthetic heart valves by suture trapping: experimental findings

The vulnerability of the Medtronic-Hall, Bj?rk-Shiley Monostrut, Duromedics, and St. Jude Medical valves to occluder immobilization by sutures was determined under static and pulsatile flow conditions. Variables were cardiac output, cross-sectional diameter of suture, type of suture (braided versus monofilament) and position of the offending suture along the circumference of the valve ring. Under static conditions, pressures, ranging from 40 to 340 mmHg and 10 to 170 mmHg, were required to decompress obstructed Medtronic-Hall and Bj?rk-Shiley Monostrut valves, respectively. As a result of different design characteristics and different occluder/orifice clearances the Medtronic-Hall valve showed its maximum opening pressure in case of interference with sutures at the axis of symmetry in both minor and major orifices, whereas for the Bj?rk-Shiley Monostrut valve this was reached in the minor orifice. Under pulsatile flow conditions, in case of interference with Prolene 2-0 suture, the Duromedics valve showed irregularly delayed opening and an opening pressure difference of 50 mmHg at a cardiac output of 8 L/min, whereas leaflet motion and pressure difference in the St. Jude Medical valve were undisturbed under similar conditions. The necessary pressure difference for opening the Medtronic Hall valve reached 44mmHg at a cardiac output of 8 L/min. High and low risk of extrinsic leaflet obstruction in the Duromedics and St. Jude Medical valves, respectively, is related to the design of the hinge mechanisms and the wedge angle of their leaflets (2 degrees versus 25 degrees). Precautionary principles in implantation of prosthetic heart valves are stressed to prevent the potentially lethal complication of occluder immobilization.(ABSTRACT TRUNCATED AT 250 WORDS)     

10-year results of anastomoses of the left internal mammary artery to the anterior interventricular artery. Angiographic and radionuclide controls

The long term patency of left internal mammary artery graft is better than that of saphenous vein graft. The aim of this study was to determined if this high patency rate was accompanied by a satisfactory myocardial perfusion. Among 143 patients treated with an internal mammary artery graft on the left anterior descending artery between 1972 and 1976, 42 patients underwent coronary angiogram and exercise tomoscintigraphy (thallium 201) over 10 years after surgery. The left internal mammary artery was patent in 92% without any atheromatous lesions. The myocardial perfusion in the area supplied by the left anterior descending artery was normal in 74%. A slight ischemia appeared during exercise in 19% without any clinical symptoms. This long term study shows excellent anatomical results correlated with a good myocardial perfusion during exercise in most cases.